Antimicrobial action of compound 48/80--II mechanism of action.

The mixture of compounds called compound 48/80 had been shown to have antimicrobial activity against a wide variety of microorganisms. In this paper it is shown that its primary site of attack appears to be on the membrane of the cell. In its presence, Tetrahymena became much more sensitive to osmotic stress, and alpha-methylglucose was rapidly released from preloaded Escherichia coli cells. The drug also had effects on cell viability, respiration, cell division, and the release of material absorbing at 260 nm. In general, its effects paralleled those of polymyxin B, although its structure is quite different except for the presence of amino groups and hydrophobic regions in both molecules. The activity of 48/80 was not due to detergent-like, surface-active properties and was antagonized by magnesium and other cations and by phosphatidylserine. Purification of the active principle might provide a relatively simple and readily modifiable probe of membrane function and possibly a new family of useful antimicrobial compounds.